Biology subjects

Venkitachalam, S.

Publications and source records attributed to Venkitachalam, S..

7 recordsLinked to original sources

bioRxiv2026

Complex-trait dissection with Evolve-and-Resequence: Selection for improved flight performance in laboratory fruit fly populations

Evolve-and-Resequence studies combine experimental evolution with molecular sequencing, enabling associations between complex trait phenotypes and evolved genomic changes. For this, a targeted complex trait is subjected to artificial laboratory selection in genetically variable populations. Using populations of fruit flies Drosophila melanogaster from the DSPR background, we have conducted a short-term selection study on a highly complex trait : flight performance. We selected for improved flight performance using a custom-built flight tunnel system, with light as a motivator and airflow as a resistive factor. As a result, flight performance significantly improved in selected populations compared to controls. We also observed signatures of evolution in flight related traits, such as activity level and wing shape, and in life-history related traits such as adult dry mass and fecundity. We used whole genome pooled sequencing on the selected and control populations, revealing significantly differentiated genomic sites. Gene ontology and enrichment analyses revealed the evolution of pathways involved in response to stimuli, growth, and development. We identified several genes of interest (e.g., Sdc, dally). The range of evolved phenotypes and associated genomic changes show that flight performance is an ideal complex trait for future Evolve-and-Resequence studies.

evolutionary biology↗

bioRxiv2023

An individual-based simulation framework exploring the ecology and mechanistic underpinnings of larval crowding in laboratory populations of Drosophila

The study of larval competition in laboratory populations of Drosophila, implemented via the crowding of larval cultures, has contributed greatly to the understanding of the ecology of competition, the evolution of larval competitive ability, and formed the basis of rigorous testing of the theory of density-dependent selection. Earlier studies led to the view that the outcomes of larval competition, and resulting evolutionary consequences of crowding-adaptation, could largely be understood by varying the starting density of individuals in a crowded culture. However, recent studies have shown that the results of adaptation to larval crowding may not be well predicted by the total larval density (i.e., total starting individuals/total volume of food). Cultures raised at the same total density but at different egg number and food volume combinations were shown to have different underlying density-specific fitness functions, and crowding-adaptation in each of these cultures was attained through different evolutionary trajectories as well. A recent study showed that cultures with not just the same density, but the same egg and food volume combination, achieved through food columns of differing diameter and height, could also differ greatly in fitness-related trait outcomes. In that study, the density of larvae in the feeding band (volume of food close to the surface in contact with air, to which larval feeding is largely restricted) was a very important factor in predicting the outcomes of larval competition. Given these recent findings, it is important to understand the overall role of feeding band density, and how it influences density-specific fitness functions in different kinds of crowded cultures. As the older models of larval competition are now insufficient to capture current empirical data, we constructed an individual-based simulation framework informed in part by these more recent findings, in order to better understand the evolutionary ecology and mechanistic underpinnings of larval competition, and predict robust experiments for expanding our understanding of the process of larval competition in Drosophila.

ecology↗

bioRxiv2023

More than just density: the role of egg number, food volume and container dimensions in mediating larval competition in Drosophila melanogaster

Flies of the genus Drosophila have been extensively used as model systems to study competition. Experiments using larval crowding in these species have furthered our understanding of competition ecology, stress-adaptation, density-dependent selection and population dynamics. Historically, larval competition has been induced by crowding the larvae in high density cultures, compared to low-density controls. However, recent studies have shown that two larval cultures having the same total eggs per mL food density, with different absolute quantities of eggs and food, can differ greatly in their density-specific fitness functions. Similarly, populations adapted to two types of cultures achieving the same density through different means, can also evolve different traits. Thus, it is clear that there is more to larval crowding than just eggs/food density, which has until now been the benchmark variable for quantifying larval crowding in Drosophila studies. In the current study, we explore the consequences of implementing crowding in different ways, using a three-way factorial experiment with egg number and food volume, cast into different food column heights or cylindrical vials with different diameters. We find that not just the same density, but cultures having the same egg number and food volume combination but experienced in food columns of varying height and diameter can have very different pre-adult survivorship and development times. We further propose a new variable for quantifying larval crowding - effective density, which is the density within the larval feeding band, a volume of food close to the surface, with access to air, wherein a majority of the larvae feed. We show that effective density is a much better predictor of the outcomes of competition than the popularly used total eggs/food density.

evolutionary biology↗

bioRxiv2023

The evolution of competitive effectiveness and tolerance in populations of Drosophila melanogaster adapted to chronic larval crowding at varying combinations of egg number and food volume

The theory of density-dependent selection posits that genotypic fitness can vary depending on the population density. Several long-term selection experiments on outbred populations of Drosophila adapted to chronically high larval densities have shown that the most common evolutionary response of such rearing is an increase in larval competitive ability. Some authors have proposed that a better understanding of the evolution of competitive ability can be achieved by its partitioning into effectiveness and tolerance components. Effectiveness is the amount of competitive inhibition imposed by a competitor on another, whereas tolerance is the degree to which a competitor can withstand inhibition. In this study, we have explored the evolution of effectiveness and tolerance components of competitive ability using three sets of outbred populations of D. melanogaster adapted to chronic larval crowding at different respective combinations of egg number, food volume and container dimensions. Effectiveness and tolerance were found to be dependent on the particular selection regime, the starting food amount and the trait used as the outcome of competition. Eclosion, dry biomass and dry weight per fly distributions over time indicated that competitive ability can also express itself in a time-dependent manner. The results suggest that larval competition and the evolution of competitive ability in Drosophila are extremely nuanced.

evolutionary biology↗

bioRxiv2023

The role of greater competitive ability in countering age disadvantages in larval competition in Drosophila melanogaster

BackgroundPopulations of Drosophila melanogaster adapted to high larval densities evolve increased larval competitive ability compared to low density controls. However, traits contributing to greater competitive ability can differ across such populations, depending on the exact details of high-density conditions imposed. In the current study, we consider three sets of D. melanogaster populations adapted to three different kinds of high-density scenarios. These population sets have evolved different degrees of increases in egg size and decreases in egg hatching time as correlates of increased larval competitive ability. QuestionWe asked two related questions: O_LIDo populations adapted to larval crowding counter an imposed initial age disadvantage in larval competition, better than their controls? C_LIO_LIDo differences in egg size and egg hatching time among crowding-adapted populations matter in competitive performance when suffering age disadvantage? C_LI Study systemWe used three sets of outbred laboratory Drosophila melanogaster populations selected for larval crowding with different egg number, food volume and vial type combinations (named MCU, CCU and LCU). We also used one set of low-density ancestral control populations (named MB). MethodsWe implemented high density cultures with half the eggs from one of the study (focal) populations, and the other half from a common marked competitor population (Orange Eye: OE). We provided head start durations of 0, 3, 5, or 7 hours to the eggs of the common competitor. This imposed the respective age disadvantage to the larvae of the focal population. Pre-adult development time of survivors was the indicator of competitive performance used. ResultsAll crowding-adapted populations countered an initial age disadvantage better than the control populations. We did not see any differences among crowding adapted populations regarding their performance in countering the age disadvantage. The common competitors showed the best competitive performance against the populations with the greatest egg size and shortest hatching time. ConclusionsAdaptation to crowding leads to significantly better chances against age disadvantages in larval competition. Temporal head starts need not be of overwhelming advantage in larval competition against superior competitors in Drosophila. Among crowding adapted populations, evolving greater egg size and shorter hatching time does not seem to better offset the effects of age disadvantage to larvae. Differences in larval effectiveness and tolerance of the populations are likely to explain these results.

evolutionary biology↗

bioRxiv2021

Density-dependent selection in Drosophila: evolution of egg size and hatching time

Many different laboratory studies of adaptation to larval crowding in Drosophila spp. have all yielded the evolution of pre-adult competitive ability, even though the ecological context in which crowding was experienced varied across studies. However, the evolution of competitive ability was achieved through different suites of traits in studies wherein crowding was imposed in slightly different ways. Earlier studies showed the evolution of increased competitive ability via increased larval feeding rate and tolerance to nitrogenous waste, at the cost of food to biomass conversion efficiency. However, more recent studies, with crowding imposed at relatively low food levels, showed the evolution of competitive ability via decreased larval development time and body size, and an increase in the time efficiency of conversion of food to biomass, with no change in larval feeding rate or waste tolerance. Taken together, these studies have led to a more nuanced understanding of how the specific details of larval numbers, food amounts etc. can affect which traits evolve to confer increased competitive ability. Here, we report results from a study in which egg size and hatching time were assayed on three sets of populations adapted to larval crowding experienced in slightly different ways, as well as their low density ancestral control populations. Egg size and hatching time are traits that may provide larvae with initial advantages under crowding through increased starting larval size and a temporal head-start, respectively. In each set of populations adapted to some form of larval crowding, the evolution of longer and wider eggs was seen, compared to controls, thus making egg size the first consistent correlate of the evolution of increased larval competitive ability across Drosophila populations experiencing crowding in slightly different ways. Among the crowding-adapted populations, those crowded at the lowest overall eggs/food density, but the highest density of larvae in the feeding band, showed the largest eggs, on an average. All three sets of crowding-adapted populations showed shorter average egg hatching time than controls, but the difference was significant only in the case of populations experiencing the highest feeding band density. Our results underscore the importance of considering factors other than just eggs/food density when studying the evolution of competitive ability, as also the advantages of having multiple selection regimes within one experimental set up, allowing for a more nuanced understanding of the subtlety with which adaptive evolutionary trajectories can vary across even fairly similar selection regimes.

evolutionary biology↗

bioRxiv2021

The EphB2-MYC Axis is a Major Determinant of Barrett's Pathobiology and a Therapeutic Vulnerability in Esophageal Cancer

Esophageal adenocarcinoma (EAC), a highly aggressive cancer with limited therapeutic options, often arises in the backdrop of a molecularly-complex esophageal metaplasia disorder, Barretts Esophagus (BE). Using transcriptomics and systems biology analyses of treatment-naive malignant/pre-malignant biopsy tissues, we found Eph receptor B2 (EphB2) tyrosine kinase signaling to be frequently hyperactivated during early stages of EAC development, and across the BE-EAC continuum. Functional studies revealed EphB2 to be an upstream post-translational regulator of c-MYC activity and as a key molecular dependency in BE/EAC. Single-cell transcriptomics in a porcine esophageal 3D spheroid model showed enhanced EphB2 and MYC activity to be significantly associated with BE-like cell fate. shRNA-based knockdown of EphB2 or small molecule inhibitors of MEK, that modulate MYC protein stability, proved effective in suppressing EAC tumor growth in vivo. These findings point to EphB2-MYC axis as an early promoter of EAC and a novel therapeutic vulnerability in this increasingly-prevalent esophageal malignancy. STATEMENT OF SIGNIFICANCEWe identify EphB2 signaling as a potential master regulator and early promoter of esophageal adenocarcinoma, and the proto-oncogene MYC as a key downstream effector of EphB2 function. Targeting the EphB2-MYC axis could be a promising therapeutic strategy for these often refractory and lethal EAC tumors.

cancer biology↗